Abstract
The present study was performed to investigate the anti-septic effects of Qi-Shao-Shuang-Gan (QSSG), a combination of Astragalus membranaceus saponins (SAM) and Paeonia lactiflora glycosides (GPL), in septic mice induced by cecal ligation and puncture. QSSG was shown to elevate the survival rate of mice, decrease infiltration of polymorphonuclear leukocytes into livers and lungs, lower serum levels of myeloperoxidase, nitric oxide, and lactate dehydrogenase, and decrease mRNA expressions of inducible nitric oxide synthase and interleukin-1β in livers. It also restored the impaired expressions of protein C (PC) mRNA in mouse livers and expressions of thrombomodulin and endothelial PC receptor mRNA in endothelial cells. Neither SAM nor GPL alone could significantly increase the survival rate of septic mice. The findings indicate that QSSG exerts protective action against polymicrobial sepsis by inhibiting systemic inflammatory response and upregulating PC pathway, and there are synergistic effects between SAM and GPL.
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Abbreviations
- QSSG:
-
Qi-Shao-Shuang-Gan
- SAM:
-
Astragalus membranaceus saponins
- GPL:
-
Paeonia lactiflora glycosides
- CLP:
-
cecal ligation and puncture
- MPO:
-
myeloperoxidase
- NO:
-
nitric oxide
- LDH:
-
lactate dehydrogenase
- iNOS:
-
inducible nitric oxide synthase
- IL-1β:
-
interleukin-1β
- PC:
-
protein C
- PMN:
-
polymorphonuclear leukocytes
- TM:
-
thrombomodulin
- EPCR:
-
endothelial PC receptor
- ALT:
-
alanine aminotransferase
- AST:
-
aspartate aminotransferase
- LPS:
-
lipopolysaccharide
- H&E:
-
hematoxylin and eosin
- w/d:
-
wet-to-dry weight ratio
- RT-PCR:
-
reverse-transcription polymerase chain reaction
- HUVECs:
-
human umbilical vein endothelial cells
References
Martin, G.S., D.M. Mannino, S. Eaton, and M. Moss. 2003. The epidemiology of sepsis in the United States from 1979 through 2000. New England Journal of Medicine 348: 1546–1554.
Seam, N., and A.F. Suffredini. 2007. Mechanisms of sepsis and insights from clinical trials. Drug Discov Today Dis Mech 4: 83–93. doi:10.1016/j.ddmec.2007.10.004.
Aird, W.C. 2003. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 101: 3765–3777. doi:10.1182/blood-2002-06-1887.
Levi, M., T. van, der, Poll, and H. R. Büller. 2004. Bidirectional relation between inflammation and coagulation. Circulation 109: 2698–2704. doi:10.1161/01.CIR.0000131660.51520.9A.
Daniel, G., and M.D. Remick. 2007. Pathophysiology of sepsis. American Journal of Pathology 170: 1435–1444. doi:10.2353/ajpath.2007.060872.
Dhainaut, J.F., N. Marin, A. Mignon, and C. Vinsonneau. 2001. Hepatic response to sepsis: interaction between coagulation and inflammatory processes. Critical Care Medicine 29: S42–S47.
Yan, S.B., J.D. Helterbrand, D.L. Hartman, T.J. Wright, and G.R. Bernard. 2001. Low levels of protein C are associated with poor outcome in severe sepsis. Chest 120: 915–922. doi:10.1378/chest.120.3.915.
Gonzalez-Rey, E., A. Chorny, G. Robledo, and M. Delgado. 2006. Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia. Journal of Experimental Medicine 203: 563–571. doi:10.1084/jem.20052017.
Xu, X.X., L.Z. Xia, and J.R. Gao. 2002. Study on antiplatelet effect of radix astragali total saponin combined with radix paeoniae rubra glucosides. Journal of Chinese Medicinal Materials 9: 653–655.
Xu, X.X., Q.Y. Liu, D.Y. Peng, L.Z. Xia, and J.R. Gao. 2002. Synergistic antithrombotic action between astragalosides and total saponins of paeonia. Chinese Journal of Experimental Traditional Medical Formulae 8: 35–38.
Li, H.B., Y.K. Ge, L. Zhang, and X.X. Zheng. 2006. Astragaloside IV improved barrier dysfunction induced by acute high glucose in human umbilical vein endothelial cells. Life Sciences 79: 1186–1193. doi:10.1016/j.lfs.2006.03.041.
Cui, R., J. He, B. Wang, F. Zhang, G. Chen, S. Yin, and H. Shen. 2003. Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats. Cancer Chemotherapy and Pharmacology 51: 75–80. doi:10.1007/s00280-002-0532-5.
Minsook, R., H.K. Eun, and C. Mison. 2008. Astragali Radix elicits anti-inflammation via activation of MKP-1, concomitant with attenuation of p38 and Erk. Journal of Ethnopharmacology 115: 184–193.
Ye, J.F., H.L. Duan, X.M. Yang, W. Yan, and X. Zheng. 2001. Anti-thrombosis effect of paeoniflorin: evaluated in a photochemical reaction thrombosis model in vivo. Planta Medica 67: 766–768.
Ruan, J.L., Z.X. Zhao, Q.Z. Zeng, and Z.M. Qian. 2003. Recent advances in study of components and pharmacological roles of Radix Paeoniae Rubra. Chinese Pharmacological Bulletin 19: 965–970.
Wichterman, K.A., A.E. Baue, and I.H. Chaudry. 1980. Sepsis and septic shock—a review of laboratory models and a proposal. Journal of Surgical Research 29: 189–201.
Ma, X.Q., Q. Shi, J.A. Duan, T.T. Dong, and K.W. Tsim. 2002. Chemical analysis of radix Astragali (Huangqi) in China: a comparison with its adulterants and seasonal variations. Journal of Agricultural and Food Chemistry 50: 4861–4866.
Huang, C.R., G.J. Wang, H. Li, H.T. Xie, J.G. Sun, and H. Lv. 2006. Sensitive and selective liquid chromatography-electrospray ionization-mass spectrometry analysis of astragaloside-IV in rat plasma. Journal of Pharmaceutical and Biomedical Analysis 40: 788–793.
Wang, S., J. Li, H. Huang, W. Gao, C. Zhuang, B. Li, P. Zhou, and D. Kong. 2009. Anti-hepatitis B virus activities of Astragaloside IV isolated from Radix Astragali. Biological and Pharmaceutical Bulletin 32: 132–135. doi:10.1248/bpb.32.132.
Xu, X.X., R. Zhang, and L.Z. Xia. 2008. Effects of three saponin extracting methods on content of astragaloside IV. Chinese Journal of Veterinary Drug 42: 12–14.
Liu, H.Q., W.Y. Zhang, X.T. Luo, Y. Ye, and X.Z. Zhu. 2006. Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson's disease by activation of adenosine A1 receptor. British Journal of Pharmacology 148: 314–325. doi:10.1038/sj.bjp.0706732.
Yang, J., Y. Dai, Y.F. Xia, W.Z. Huang, and Z.T. Wang. 2009. Alpinia katsumadai Hayata prevents mouse sepsis induced by cecal ligation and puncture through promoting bacterial clearance and downregulating systemic inflammation. Phytother Res 23: 267–273. doi:10.1002/ptr.2610.
Hotchkiss, K.A., A.W. Ashton, R. Mahmood, R.G. Russell, J.A. Sparano, and E.L. Schwartz. 2002. Inhibition of endothelial cell function in vitro and angiogenesis in vivo by docetaxel (taxotere): association with impaired repositioning of the microtubule organizing center. Mol Cancer Ther 1: 1191–1200.
Russell, J.A. 2006. Management of sepsis. New England Journal of Medicine 355: 1699–1713.
Vincent, J.L., H. Zhang, C. Szabo, and J.C. Preiser. 2000. Effects of nitric oxide in septic shock. American Journal of Respiratory and Critical Care Medicine 161: 1781–1785.
Bultinck, J., P. Sips, L. Vakaet, P. Brouckaert, and A. Cauwels. 2006. Systemic NO production during (septic) shock depends on parenchymal and not on hematopoietic cells: in vivo iNOS expression pattern in (septic) shock. FASEB Journal 20: E1619–E1627. doi:10.1096/fj.06-5798fje.
Guidet, B., P. Aeqerter, R. Gauzit, P. Meshaka, D. Dreyfuss, and CUB-Rea, Study, Group. 2005. Incidence and impact of organ dysfunctions associated with sepsis. Chest 127: 942–951. doi:10.1378/chest.127.3.942.
Pinsky, M.R., J.L. Vincent, J. Deviere, M. Alegre, R.J. Kahn, and E. Dupont. 1993. Serum cytokine levels in human spetic shock: Relation to multiple system organ failure and mortality. Chest 103: 562–575.
Shorr, A.F., G.R. Bernard, J.F. Dhainaut, J.R. Russell, W.L. Macias, and D.R. Nelson. 2006. Protein C concentrations in severe sepsis: an early directional change in plasma levels predicts outcome. Cril Care 10: R92. doi:10.1186/cc4946.
Esmon, C.T. 2003. The protein C pathway. Chest 124: S26–S32. doi:10.1186/cc6155.
Joyce, D.E., L. Gelbert, A. Ciaccia, B. Dehoff, and B.W. Grinnell. 2001. Gene expression profile of antithrombotic protein C defines new mechanisms modulating inflammation and apoptosis. Journal of Biological Chemistry 276: 11199–11203.
Acknowledgment
This work was supported by the National Natural Science Foundation of China (no. 30600821), the Natural Science Foundation of Anhui Province (no. 050431004), and the Postgraduate Innovation Project of Jiangsu Province.
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Gao, Xh., Xu, Xx., Pan, R. et al. Qi-Shao-Shuang-Gan, a Combination of Astragalus membranaceus Saponins with Paeonia lactiflora Glycosides, Ameliorates Polymicrobial Sepsis Induced by Cecal Ligation and Puncture in Mice. Inflammation 34, 10–21 (2011). https://doi.org/10.1007/s10753-010-9202-7
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DOI: https://doi.org/10.1007/s10753-010-9202-7